Work will be conducted jointly at the Massachusetts Institute of Technology and at the University of Pittsburgh. Specific tasks which will be performed at each location under the direction of Wells and Griffith are summarized below. Work to be performed at University of Pittsburgh (A. Wells Laboratory): 1. Activation of select signaling pathway downstream from EGFR will be quantified in the undifferentiated MSC (Aim 1). 2. Activation of select signaling pathway downstream from EGFR will be quantified in the pre-differentiated MSC (Aim 2). 3. Production of autocrine ligands will be quantified with the MSC on various surfaces (Aim 2). 4. Differentiation of MSC while on the various surfaces into at least 3 lineages (Aim 3). Work to be performed at MIT (L. Griffith and P. Hammond Laboratory): 1. Synthesis of t-EGF substrates (Aims 1-3). Similar substrates have been successfully mailed these substrates to Pittsburgh and other labs and maintained their activity. 2. Analysis of apoptosis (Aim 1) and proliferation (Aim 2) via FACS 3. Synthesis of substrates for specialized migration/differentiation studies (Aim 3) These tasks will be coordinated by frequent telephone and electronic communications, facilitated by compatible computer software. This will promote data sharing and interpretation by all involved. All major planning will be done at semi-annual visits by the Investigators;as has been accomplished since 1994. The most recent meeting occurred in Cambridge in January 2007. This frequent visiting is further facilitated by serving on the thesis committees of each other's graduate students. Lastly, trainees will be exchanged for extended periods to learn complementary techniques and approaches;this `sharing'of trainees has been used to great advantage.